Cobalt chloride-mediated protein kinase Cα (PKCα) phosphorylation induces hypoxia-inducible factor 1α (HIF1α) in the nucleus of gastric cancer cell

2016 ◽  
Vol 471 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Suvasmita Rath ◽  
Aditya Anand ◽  
Nilabh Ghosh ◽  
Lopamudra Das ◽  
Shrikant B. Kokate ◽  
...  
Author(s):  
Bing Zhang ◽  
Chun Xia

AbstractThe PKB signaling pathway is essential for cell survival and the inhibition of apoptosis, but its functional mechanisms have not been fully explored. Previously, we reported that TPA effectively inhibited PKB activity and caused PKB degradation, which was correlated with the repression of PKB phosphorylation at Ser473. In this study, we focus on how PKB is regulated by TPA in gastric cancer cells. One of the TPA targets, PKCα, was found to mediate the inhibition of PKB phosphorylation and degredation caused by TPA. Furthermore, TPA induced the import of PKCα into the nucleus, where PKCα exerted an inhibitory effect on PKB expression and phosphorylation. As a result, cancer cell proliferation was arrested. Our study characterizes a novel function of PKCα in mediating the negative regulation of PKB by TPA, and suggests a potential application in the clinical treatment of gastric cancer.


Author(s):  
Bing Zhang ◽  
Chun Xia

AbstractProtein kinase B (PKB/Akt) is a serine-threonine kinase functioning downstream of phosphatidylinositol 3-kinase (PI-3 kinase) in response to mitogen or growth factor stimulation. In several cell types, it plays an important anti-apoptotic role. TPA is a potent regulator of the growth of many different cell types. Here, we detected that TPA could induce cell apoptosis in the gastric cancer cell line, BGC-823. We also found that TPA inhibited the expression of PKB/Akt in a TPA concentration- and time-dependent manner. Furthermore, TPA inhibited the phosphorylation of PKB at Ser473, but did not affect the phosphorylation of Thr308. It only attenuated the expression of PKB/Akt and the phosphorylation of Ser473 in the cell nucleus, whereas it did not change the PKB/Akt distribution in BGC-823 cells. These results suggest that PKB/Akt inhibition by TPA may be the important factor in the mechanism of effect of TPA on gastric cell lines.


Pathobiology ◽  
2005 ◽  
Vol 72 (3) ◽  
pp. 152-159 ◽  
Author(s):  
Yoshihiko Iioka ◽  
Kenji Mishima ◽  
Nakanobu Azuma ◽  
Akihiko Tsuchida ◽  
Yu Takagi ◽  
...  

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